ArticleCell death & disease2011
C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- 3D matrix stiffness drives energy metabolism to orchestrate stem cell osteogenesis via microtubule acetylation and mitochondrial dynamics.Bioactive materials · 2026Article
- Targeting cell membrane sphingolipids: a novel ceramide analog CeY-B1 inhibits migration and invasion in cervical cancer cells.Journal of translational medicine · 2026Article
- Targeting ceramide metabolism to restore hypoxia-induced apoptosis in p53-deficient colon cancer cells.PloS one · 2026Article
- Selective Knockdown of Ceramide Synthases Reveals Opposite Roles of Different Ceramide Species in Cardiac Homeostasis.Metabolites · 2025Article
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- AGBL2 promotes renal cell carcinoma cells proliferation and migration via α-tubulin detyrosination.Heliyon · 2024Article
- Lipid-Based Nanoparticles Fused with Natural Killer Cell Plasma Membrane Proteins for Triple-Negative Breast Cancer Therapy.Pharmaceutics · 2024Article
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Ceramide Kinase Inhibition Drives Ferroptosis and Sensitivity to Cisplatin in Mutant KRAS Lung Cancer by Dysregulating VDAC-Mediated Mitochondria Function.Molecular cancer research : MCR · 2022Article
- Alkaline ceramidase catalyzes the hydrolysis of ceramides via a catalytic mechanism shared by Zn2+-dependent amidases.PloS one · 2022Article
- Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells.International journal of nanomedicine · 2022Article
- Ceramides bind VDAC2 to trigger mitochondrial apoptosis.Nature communications · 2019Article
- FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer.Cancer letters · 2018Article
- Sphingolipid metabolism and drug resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency.Drug delivery · 2017Article
- A novel mechanism of ERK1/2 regulation in smooth muscle involving acetylation of the ERK1/2 scaffold IQGAP1.Scientific reports · 2017Article
- MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling.Oncotarget · 2017Article
- Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling.Oncotarget · 2016Article
- Pre-clinical characterization of PKC412, a multi-kinase inhibitor, against colorectal cancer cells.Oncotarget · 2016Article
- C6 ceramide sensitizes the anti-hepatocellular carcinoma (HCC) activity by AZD-8055, a novel mTORC1/2 dual inhibitor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.